1. Field of the Invention
The invention relates to the field of treating cancer.
2. Background
In 1628, William Harvey first demonstrated the heart was a pump, pushing blood to the lungs for oxygenation, and then through the peripheral vascular system to bring oxygen and nutrients to every cell in the body. It was another 350 years before the heart was established as an endocrine gland. This discovery was stimulated by the experiments of deBold et al. who infused extracts of atria of rat hearts into other rats which resulted in a 10-fold increase in water excretion and 30-fold increase in sodium excretion. It is now known that there are a number of peptide hormones synthesized within the heart and this family is called atrial natriuretic peptides (ANPs). These peptides were so named because they are synthesized mainly in the atria of the heart and one of their main biologic functions is to enhance sodium excretion (i.e., natriuresis). Atrial natriuretic peptides are synthesized by three different genes and then stored as three different prohormones (i.e., 126 amino acid [a.a.] atrial natriuretic peptide (ANP), 108 a.a. brain natriuretic peptide (BNP), and 126 a.a. C-natriuretic peptide (CNP) prohormones). Atrial natriuretic peptide, further, is part of a hormonal system in which one gene synthesizes four peptide hormones (FIG. 1). The ANP gene synthesizes a 151 preprohormone which is processed within the endoplasmic reticulum to form a 126 a.a. prohormone (i.e., the storage form of the following peptide hormones) after removal of a 25 a.a. signal peptide from its N-terminal end (FIG. 1).
These four peptide hormones within the 126 a.a. ANP prohormone consist of:
(1) the first 30 amino acids from the N-terminal end of the prohormone (i.e., proANP 1-30; long acting natriuretic peptide, LANP);
(2) a.a. 31-67 (i.e., proANP 31-67; vessel dilator);
(3) a.a. 79-98 (proANP 79-98; kaliuretic peptide); and(4) a.a. 99-126 (ANP) of this prohormone (FIG. 1).
Each of these four peptide hormones circulate within the blood stream with LANP and vessel dilator's concentrations in plasma being 15- to 20-fold higher than ANP. Each of these peptide hormones have biologic effects, e.g., blood pressure lowering, natriuretic and/or diuretic effects in both animals and humans.